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Objective Pemetrexed plus carboplatin offers survival advantage in first line treatment of advanced lung cancer patients with performance status of 2. We estimated the cost-effectiveness of this combined regimen compared to pemetrexed alone in a Brazilian population. Methods A cost-effectiveness analysis was conducted based on a randomized phase III trial in patients with advanced non-small cell lung cancer (NSCLC) and ECOG performance status of 2 (PS2), comparing doublet regimen pemetrexed plus carboplatin with pemetrexed alone. The perspective adopted was the public health care sector over a three-year period. Direct medical costs and survival time were calculated from patient-level data and utility values were extracted from the literature. Sensitivity analyses were performed to evaluate uncertainties in the results. Results and conclusion The combined regimen pemetrexed plus carboplatin yielded a gain of 0.16 life year (LY) and 0.12 quality-adjusted life year (QALY) compared to pemetrexed alone. The total cost was 17,674.31 USD for the combined regimen and 15,722.39 USD for pemetrexed alone. The incremental cost-effectiveness ratio (ICER) was $12,016.09 per LY gained and $15,732.05 per QALY gained. The factors with the greatest impact on the ICER are pemetrexed price and the time to progression utility value. The cost-effectiveness acceptability curve showed an upper 90% probability of pemetrexed plus carboplatin being cost-effective with a threshold between two and three GDP per capita. Our study suggests superiority of the combined pemetrexed plus carboplatin regimen in terms of efficacy as well as cost-effectiveness in advanced NSCLC patients with a poor performance status of 2.